Protein production starts by first defining what protein you want to produce. Such proteins selected are used to treat specific diseases. The drug development steps for the discovery and production of novel protein drug candidates are:
Target identification
The first step of drug discovery is to identifying the biological origin of a disease, and the potential targets for intervention.
Target validation
The second step of the drug discovery process is to prove if an identified target is directly involved in a specific disease and if modulation of this target is likely to have a therapeutic effect.
Hit identification and lead generation (H2L)
The next early drug discovery step utilizes a high throughput screening (HTS) process to evaluate and optimize promising lead compounds previously identified as potential targets. These lead compounds undergo more extensive optimization in subsequent steps of drug discovery in the lead optimization (LO) step.
Lead optimization
The objective of this drug discovery phase is to synthesize the lead compounds in order to improve properties. Lead optimization includes experimental testing for the confirmation of the identified compound(s). Optimization refers to optimizing binding affinity, selectivity and/or efficacy. Once this process is confirmed, these drug candidates can be registered or patented for intellectual property protection.
Preclinical testing
In this preclinical step it is vital to determine if the drug candidate has promising activity against the biologic target relevant to the disease of interest. Additionally, sufficient safety and drug-like properties prior to human testing must be identified. Defining safe dosing for human studies is a key aspect of preclinical testing process.
Preclinical results can be submitted to regulatory authorities (e.g. US - FDA) as an Investigational New Drug (IND) and must be finalized before moving to the clinical phase.
Clinical phase
Clinical studies consist of 4 phases:
- Phase I – first human studies – mainly safety testing on healthy persons
- Phase II – testing different doses on patients
- Phase II – expand test panel, efficacy, and meet primary and secondary endpoints
- Phase IV – post marketing safety study, tackle safety concerns, different populations, and sometimes-rare side effects
Market ready
When the biologic is approved for market release; protein production on a large scale is required.
Which expression system to choose for protein production
Many organisms can produce proteins. See the table below for major organisms and important cellular characteristics.